Nitroimidazole anti-infectives represent a class of agents employed in the treatment of individuals suffering from a variety of infections. Metronidazole, a member of the nitroimidazole anti-infectives class, has been used in the treatment of individuals suffering from anaerobic infections, intra-abdominal infections, skin and skin structure infections, gynecologic infections, bacterial septicemia, bone and joint infections, CNS infections, respiratory tract infections, endocarditis caused by Bacteroides species, amebiasis, trichomoniasis, bacterial vaginosis, acne rosacea, hepatic encephalopathy, Crohn's disease, diarrhea associated with Clostridium difficile, Heliobacter pylori infections, recurrent urethritis, and pelvic inflammatory disease.
With respect to Crohn's disease, for example, metronidazole is active against anaerobic bowel flora and has been used for prophylaxis and treatment of patients suffering from this disease. Although a cause and effect relationship has not been established, Crohn's disease patients who have been treated with metronidazole at high doses for extended periods of time have been known to have an increased incidence of certain extraintestinal cancers, such as breast cancer. In view of the general desire to limit the exposure of xenobiotics only to affected tissues generally, and in view of the potential for extraintestinal side effects caused by metronidazole-based pharmacotherapy in the treatment of patients suffering from Crohn's disease in particular, it would be desirable to have a drug that has decreased exposure extra-intestinally while possessing nitroimidazole anti-infective activities and/or have other advantages.
The present invention seeks to address these and other needs in the art.